Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 24, 2023

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here, we used millimeter-scale volumetric electron microscopy 1 to investigate all inhibitory neurons across densely-segmented population 1352 cells spanning layers mouse visual cortex, producing wiring diagram connections more than 70,000 synapses. Taking data-driven approach inspired by classical neuroanatomy, classified based on relative targeting dendritic compartments other developed novel classification excitatory morphological synaptic input The between revealed class disinhibitory specialist basket cells, addition familiar subclasses. Analysis onto found widespread specificity, many interneurons exhibiting differential certain subpopulations spatially intermingled potential targets. Inhibitory was organized into “motif groups,” diverse sets that collectively target both perisomatic same Collectively, our analysis identified new organizing principles for inhibition will serve as foundation linking modern multimodal atlases diagram.

Язык: Английский

---

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

Science, Год журнала: 2023, Номер 382(6667)

Опубликована: Окт. 12, 2023

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion human neocortex marked by distinctive pyramidal neurons with extensive L1 branching, but whether interneurons are similarly diverse underexplored. Using Patch-seq recordings from neurosurgical tissue, we identified four transcriptomic subclasses mouse homologs, along distinct subtypes types unmatched in L1. Subclass subtype comparisons showed stronger differences were correlated strong morphoelectric variability dimensions variability. Accompanied greater thickness other cytoarchitecture changes, these findings suggest that has diverged evolution, reflecting the demands regulating expanded neocortical circuit.

Язык: Английский

---

Inhibitory specificity from a connectomic census of mouse visual cortex

Nature, Год журнала: 2025, Номер 640(8058), С. 448 - 458

Опубликована: Апрель 9, 2025

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate all inhibitory neurons across densely segmented population 1,352 cells spanning layers mouse visual cortex, producing wiring diagram inhibition more than 70,000 synapses. Inspired by classical neuroanatomy, classified based on targeting dendritic compartments developed an excitatory neuron classification reconstructions whole-cell maps synaptic input. Single-cell showed class disinhibitory specialist that targets basket cells. Analysis onto found widespread specificity, many interneurons exhibiting differential spatially intermingled subpopulations. Inhibitory was organized into 'motif groups', diverse sets collectively target both perisomatic same targets. Collectively, our analysis identified new organizing principles for will serve as foundation linking contemporary multimodal atlases diagram.

Язык: Английский

---

Genetically Defined Subtypes of Somatostatin-Containing Cortical Interneurons

eNeuro, Год журнала: 2023, Номер 10(8), С. ENEURO.0204 - 23.2023

Опубликована: Июль 18, 2023

Inhibitory interneurons play a crucial role in proper development and function of the mammalian cerebral cortex. Of different inhibitory subclasses, dendritic-targeting, somatostatin-containing (SOM) may be most diverse. Earlier studies used GFP-expressing recombinase-expressing mouse lines to characterize genetically defined subtypes SOM by morphologic, electrophysiological, neurochemical properties. More recently, large-scale classified into 13 morpho-electric transcriptomic (MET) types. It remains unclear, however, how these various classification schemes relate each other, experimental access MET types has been limited scarcity specific driver lines. To address issues, we crossed Flp Cre with dual-color intersectional reporter, allowing several combinatorially subsets. Brains from adult mice both sexes were retrogradely dye labeled pial surface identify layer 1-projecting neurons immunostained against marker proteins, revealing correlations between genetic label, axonal target, protein expression same neurons. Lastly, using whole-cell recordings

Язык: Английский

---

Cell-Type–Specific Effects of Somatostatin on Synaptic Transmission in the Anterior Cingulate Cortex

Journal of Neuroscience, Год журнала: 2024, Номер 44(13), С. e0598232024 - e0598232024

Опубликована: Фев. 20, 2024

Inhibitory modulation of glutamatergic information processing is a prerequisite for proper network function. Among the many groups interneurons (INs), somatostatin-expressing (SOM-INs) play an important role in maintenance physiological brain activity. We have previously shown that somatostatin (SOM) causes reduction pyramidal cell (PC) excitability. However, mechanisms action peptide on cortical synaptic circuits are still unclear. To understand effects neuropeptide SOM circuits, we performed detailed side-by-side comparison its postsynaptic PCs, SOM-INs, and layer 1 (L1-INs) anterior cingulate cortex male female mice found produced pronounced PCs while having little to no effect either IN type. This allowed us link observed SOM-induced modulations GABAergic transmission trace impact neuronal circuitry between these three types. show here depresses via presynaptic mechanism exerting differential GABA A receptor- B receptor-mediated at pre- level resulting shift inhibition L2/3 from L1-INs SOM-INs. In summary, this study unravels novel aspect by which modulates signaling L1-INs,

Язык: Английский

---

Dynamic regulation of cortical interneuron wiring

Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 102980 - 102980

Опубликована: Фев. 26, 2025

Язык: Английский

---

Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following discovery they predominantly function by inhibiting dendritic-targeting somatostatin (SST) disinhibiting PCs. This VIP-SST disinhibitory motif is observed throughout neocortex from mice humans, serves as a key mechanism for top-down (feedback) context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found play an important role in sensory processing, executive functions, attention, sensorimotor integration cortico-cortical thalamocortical feedback interactions. Furthermore, implicated mediating effects reinforcement signals, both reward aversive, via their responsiveness neuromodulators such acetylcholine (ACh), facilitating synaptic plasticity learning. While it evident transcriptomic analyses molecularly heterogeneous group, physiological significance this diversity unclear at present. Here, we characterized functional primary somatosensory cortex leveraging intersectional genetic approaches study IN subtypes. We can be divided into four different populations: group expresses Ca 2+ -binding protein calretinin (CR), two groups express cholecystokinin (CCK), does not either CR or CCK (non-CCK non-CR; nCCK nCR). neurons each exhibit laminar distributions, axonal dendritic arbors, intrinsic electrophysiological properties, efferent connectivity, VIP/CR target almost exclusively SST VIP/nCCK nCR also mainly but connections parvalbumin (PV) INs. These essentially no connectivity (PCs). On hand, VIP/CCK PCs, differ degree which release type modulated endocannabinoids. long-range inputs differentially recruit groups. Intriguingly, find populations subtypes turn, indicating presence specialized subcircuits. Activation subpopulations vivo results differential on network, thus providing evidence modularity actions during

Язык: Английский

---

Integrating endocannabinoid signaling, CCK interneurons, and hippocampal circuit dynamics in behaving animals

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

---

Functional diversities within neurons and astrocytes in the adult rat auditory cortex revealed by single-nucleus RNA sequencing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 20, 2024

Abstract The mammalian cerebral cortex is composed of a rich diversity cell types. Cortical cells are organized into networks that rely on their functional to ultimately carry out variety sophisticated cognitive functions. To investigate the breadth transcriptional diverse types in sensory cortex, we have used single-nucleus RNA sequencing (snRNA-seq) auditory adult rat. A unique excitatory and inhibitory neuron were identified. In addition, report for first time astrocytes may represent functionally subtypes. Together, these results pave way building models how neurons work concert with at synapses fulfill high-cognitive functions like learning memory.

Язык: Английский

---

Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июль 2, 2024

Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their ‘volume transmission’ output property. However, activity and function within circuits remain unclear. Here, we developed two genetic tools to target these neurons examine in the primary visual cortex. We found that spontaneous neurogliaform positively correlated with locomotion. Silencing increased during locomotion impaired responses L2/3 pyramidal neurons. Furthermore, contrast-dependent response varies laminar location is constrained by morphology input connectivity. These findings demonstrate importance regulating behavioral state-dependent indicate functional engagement stimuli influenced positioning

Язык: Английский

---